Charles W. Leffler, PhD

Education

• PhD Institution: University of Florida, Department of Zoology
• Postdoctoral: University of Florida, Department of Physiology

Links

Physiology - Charles Leffler

Research Interests

Research in the laboratory concentrates on control of newborn cerebral circulation. A focus of this research is control of the newborn cerebral microvasculature during physiological and pathological situations, and the cellular mechanisms involved in such control. We investigate autocrine and paracrine communication within the neurovascular unit, with specific current focus on two novel, endogenously produced, gaseous transmitter molecules, carbon monoxide (CO) and hydrogen sulfide (H2S). This research is important because the single most prominent cause of mortality and morbidity in newborns is hypoxic-ischemic brain injury, which often leads to lifelong disability in survivors. The neonatal brain is more susceptible to injury from insufficient or inappropriate blood flow for metabolism than that of the adult because of rapid development and proliferation of neurons and vessels, and high susceptibility to inflammation. Successes in developing approaches to avert and treat perinatal hypoxia-ischemic brain damage have been limited by insufficient understanding of the mechanisms that control perinatal cerebral circulation. The gasotransmitters, CO and H2S, are mechanisms of which greater understanding is urgently needed.

Representative Publications

• Patel S, Fedinec AL, Liu J, Weiss MA, Pourcyrous M, Harsono M, Parfenova H, Leffler CW. H(2)S mediates the vasodilator effect of endothelin-1 in the cerebral circulation. Am J Physiol Heart Circ Physiol. 2018 Dec 1;315(6):H1759-H1764. doi: 10.1152/ajpheart.00451.2018. Epub 2018 Sep 28. PubMed PMID: 30265150; PubMed Central PMCID: PMC6336977.
• Parfenova H, Pourcyrous M, Fedinec AL, Liu J, Basuroy S, Leffler CW. Astrocyte-produced carbon monoxide and the carbon monoxide donor CORM-A1 protect against cerebrovascular dysfunction caused by prolonged neonatal asphyxia. Am J Physiol Heart Circ Physiol. 2018 Oct 1;315(4):H978-H988. doi: 10.1152/ajpheart.00140.2018. Epub 2018 Jul 20. PubMed PMID: 30028198; PubMed Central PMCID: PMC6230909.
• Pourcyrous M, Chilakala S, Elabiad MT, Parfenova H, Leffler CW. Does prolonged severe hypercapnia interfere with normal cerebrovascular function in piglets? Pediatr Res. 2018 Aug;84(2):290-295. doi: 10.1038/s41390-018-0061-5. Epub 2018 May 28. PubMed PMID: 29907849; PubMed Central PMCID: PMC6185793.
• Liu J, Pourcyrous M, Fedinec AL, Leffler CW, Parfenova H. Preventing harmful effects of epileptic seizures on cerebrovascular functions in newborn pigs: does sex matter? Pediatr Res. 2017 Nov;82(5):881-887. doi: 10.1038/pr.2017.152. Epub 2017 Aug 16. PubMed PMID: 28665933; PubMed Central PMCID: PMC5645245.
• Harsono M, Pourcyrous M, Jolly EJ, de Jongh Curry A, Fedinec AL, Liu J, Basuroy S, Zhuang D, Leffler CW, Parfenova H. Selective head cooling during neonatal seizures prevents postictal cerebral vascular dysfunction without reducing epileptiform activity. Am J Physiol Heart Circ Physiol. 2016 Nov 1;311(5):H1202-H1213. doi: 10.1152/ajpheart.00227.2016. Epub 2016 Sep 2. PubMed PMID: 27591217; PubMed Central PMCID: PMC5130497.
• Chang J, Fedinec AL, Kuntamallappanavar G, Leffler CW, Bukiya AN, Dopico AM. Endothelial Nitric Oxide Mediates Caffeine Antagonism of Alcohol-Induced Cerebral Artery Constriction. J Pharmacol Exp Ther. 2016 Jan;356(1):106-15. doi: 10.1124/jpet.115.229054. Epub 2015 Nov 10. PubMed PMID: 26555891; PubMed Central PMCID: PMC4702074.

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